CRUK Lung Cancer Conference 2022

Key topics raised at the conference

• Screening, early detection and minimal residual disease  
• Lung cancer in never smokers  

• Metabolism and immunology in small cell lung cancer  
• Application of imaging and radiotherapy  
• Informatics and technology approaches to diagnosis and treatment  
• Immune regulation and exploitation  

Day one: “We’re back”

Professor Caroline Dive from the Manchester CRUK Lung Cancer Centre of Excellence opened the 2022 Lung Cancer Conference with a reflective look back on how far we have come. Her outlook was brilliantly positive, with a vision of a hopeful future for lung cancer as a priority for CRUK.  

Established in 2015, Caroline noted the great progress the Lung Cancer Centre has made, with the centre now enabling development across four research themes: Clinical Translation and Biomarkers, Pathology, Informatics and Pre-Clinical Models. Her talk gave a brilliant overview of the effort’s researchers in Manchester, and across the country, are making to face the significant challenges ahead together. 

Keynote: Christine Berg, US National Institute   

Christine Berg delivered the first of the conference’s keynote lectures on ‘Lung cancer screening: Current status and challenges ahead’. Christine spoke dynamically about where we stand with lung cancer risk factors beyond age and smoking, noting:  

• Air pollution is the second leading cause of lung cancer worldwide  

• We have a much better understanding of genetics related to the development of lung cancer, but testing for germline mutations needs to be more common  
• Asymptomatic carriers of germline mutations should be screened for lung cancer 
• There is a high lung cancer burden in the US, with only 5% of those most at risk being screened  
• The NHS goals are ambitious, with an aim to get 75% of people diagnosed at stage one or two 
• The targeted lung health check is a great way of screening underserved populations; however, there are challenges with delivery through limited availability of CT scanners 

• More work needs to be done on genomics, AI and biomarkers 
• We need a better understanding of lung cancer in never smokers  

Other talks throughout the day included Immune Regulation and Exploitation, chaired by Santiago Zelenay, CRUK Manchester Institute and The Big Question Panel: How do we best respond to the transformative stage shift underway in the ED of Lung Cancer? featuring Caroline Dive.  

Key take aways:  

• We need to better understand the basic biology of lung cancer lesions  
• There’s an imperative to understand the risks of different types of tobacco use  

• We are yet to realise the impact that the pandemic has had on lung cancer  
• We can learn from the COVID-19 vaccine uptake to use a social push for lung cancer screening  

Lung cancer in never smokers: Chaired by Charles Swanton from CRUK Lung Cancer Centre of Excellence, London 

This session was a personal favourite of mine, as lung cancer in never smokers is a topic I have seldom heard about.  

William Hill from The Francis Crick Institute led this session with his talk on the link between air pollution, and other environmental carcinogens, and EGFRm mutant lung cancer.  

Key take aways:  

• There is a geographical distribution of EGFR mutant lung cancer and high levels of air pollution  
• With a particulate matter (PM) 2.5 there is a positive association of EGFR lung cancer incidence in South Korean and Taiwanese populations  
• There is no association between radon and EGFRm lung cancer incidence  

• PM increases the number of EGFRm cells that go on to form a lesion, and further promotes growth of those cells  
• PM-exposed macrophages elicit a response in EGFRm cells
• Cancer mutations increase with age in normal lungs of never smokers 

Other talks in this session covered molecular drivers and cell of origin in non-small cell lung cancer (NSCLC), macrophages in NSCLC and the APOBEC3B mutation in lung cancer.  

Day Two:
Application of Imaging and Radiotherapy

Chaired by Corinne Faivre-Finn from The Christie NHS Foundation Trust 

Corinne opened the session by discussing the importance of imaging and radiotherapy in lung cancer treatment. She highlighted that:  

• Imaging is linked to radiotherapy and used to make decisions as to whether a patient with lung cancer can have radiotherapy  

• We are able to track patient treatment response with imaging modalities  
• There have been exciting progressions in imaging over the last few years 

Talks in this session covered topics such as: proton beam therapy, radiopharmaceuticals, longitudinal imaging, imaging therapy resistance in cancer and solving unmet clinical needs. 

The role of proton radiotherapy for patients with lung cancer
By Crispin Hiley, University College London  

Key take aways:  

• In 2012 the NHS confirmed the commission of two national proton beam therapy (PBT) centres; one in Manchester and one in London  
• Proton beam therapy delivers a uniform dose to the tumour and has a reduced exit dose in comparison to radiotherapy (RT) 
• Mesothelioma which occurs in nearly 7,000 patients a year was previously thought to be radiation resistant but has recently been shown to respond positively to RT; the issue with RT administration is that with a cancer of this type, large volumes require treatment and thus there can be large amounts of RT associated damage  
• PBT has been shown to be effective in the treatment of this cancer as it permits treatment of large volumes  

Fireside chat: Patient involvement in research design with Ruth Strauss foundation  

The fireside chat was my personal highlight of this conference, giving the spotlight to patients and focusing on patient struggles. While I found this to be a very emotional talk, it was simultaneously motivating in shedding light on stigmas around lung cancer and the need to eradicate them.  

We heard from Cameron Millar and Gini Harrison in this patient involvement session where they talked about their experiences of being diagnosed with lung cancer as never smokers.  

Cameron is a stage four lung cancer patient who was diagnosed in 2020. He is ALK positive which is caused by a mutation of the ALK gene and leads to the development of lung cancer.  

Gini is coming up to her first ‘cancerversary’. Her diagnosis was nine months from her first and only symptom which was shoulder pain. Her cancer was an accidental finding on an MRI. She didn’t realise you could get cancer as a never smoker and later found out she was positive for an EGFR mutation linked to the development of lung cancer.  

Both patients recited tales of being misdiagnosed, long waits for correct diagnoses, misinformation and stigma.  

Take home messages included:  

• 15% of lung cancer patients are never smokers, and this percentage is growing  
• The need to remove the association between lung cancer and smoking  
• This stigma is seen in GP surgeries where GPs have been known not to refer never smokers for a low dose CT scan to check for lung cancer 
• This is resulting in late-stage presentation of lung cancer in never smokers  

• It is hoped the TRACERx study will help to shed light on the environmental factors that contribute to the development of lung cancer and break down these stigmas  

Keynote Lecture: Monte Winslow, Stanford University School of Medicine  

Monte covered multiplex functional lung cancer genomics, focusing specifically on carcinogenesis, molecular mechanisms of metastasis, unbiased genomic and pharmacological analysis, genome engineering methods development and functional analysis of key drivers.  

They referred specifically to their modelling of lung adenocarcinoma and understanding which genes drive different phenotypes of this cancer.  

Future leaders showcase  

Chaired by Professor Caroline Dive  

In this session, we heard from Maria Peiris-Pagès from Cancer Research Manchester Institute on “Mapping the metastatic cascade to the brain in small cell lung cancer” as she talked about the need for addressing brain metastasis in small cell lung cancer (SCLC).  

Advances in Small Cell Lung Cancer  

Chaired by Katherine Simpson from CRUK Manchester Institute  

This session covered topics such as:  

• Tumour evolution and treatment resistance 
• Response and survival in small cell lung cancer  
• New opportunities for precision medicine in small cell lung cancer  
• The immunology of small cell lung cancer  

Oliver Bartley from CRUK Manchester Institute gave the proffered talk in this session, covering: “Circulating tumour cell-derived explant (CDX) models to investigate the immunology of small cell lung cancer.” 

Day Three: Informatics and technology approaches to diagnosing and treating  

Chaired by Nicky McGranahan from UCL Cancer Institute

This session kicked off the third and final day of the CRUK Lung Cancer Conference. Chaired by Nicky McGranahan from UCL Cancer Institute and featuring Simon Pearce from CRUK Manchester institute.  

Their talk focused on:  

• Subtyping of small cell lung cancers 
• cfDNA methylome profiling  
• Liquid biopsies in small cell lung cancer  
• Using cfDNA methylation as a biomarker in small cell lung cancer 

Keynote lecture: Ramaswamy Govindan, Washington University in St Louis  

In this keynote, Ramaswamy discussed the proteogenomic alterations in lung cancer, focusing specifically on lung adenocarcinoma, lung squamous cell carcinoma, relapsed small cell cancer and the challenges and opportunities in lung cancer.  

Screening, Early Detection and Minimal Residue Disease  

This session was chaired by Sam Janes from University College London Hospital, featuring our very own Phil Crosbie from CRUK Manchester Centre.   

Phil’s talk covered “Implementation of Lung Cancer Screening” and covered the Lung Health Check.  

Key take aways included:  

• The burden of lung cancer is three times higher in deprived communities  
• The lung health check acted to address this burden and take screening to these underserved communities  

• Two key interventions included: preventing smoking and screening of attendees with a low dose CR scan  
• This led to a transformation in the screening graph from stage four presentation to stage one 
• The UK National Screening Committee showed that this screening was cost-effective and recommended the introduction of targeted lung cancer screening across the UK  
• The MOPED initiative (mobile cancer prevention and early detection) is now looking at integrating other screening services, such as cervical screens, into this process 

Panel Discussion: Translation and Entrepreneurship  

The final session of the conference was an interactive discussion about translating discovery research into the clinic. We heard from Joely Irlam from the University of Manchester, who is a Research Associate in the Translational Radiotherapy Group. She talked about the spin-out of ManTRA DX which she co-founded with Professor Catharine West and the help of Cancer Research Horizons. Her take home message was that spinning out is a requirement to get the investment you need to develop your product.  

Conclusions  

We thoroughly enjoyed the experience of this face-to-face conference, and it has inspired many conversations as well as providing numerous learnings. Thank you ever so much to everyone involved, it has been truly brilliant!